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“Madness and Memory is the story of one of the most important discoveries in recent medical history, and it is also a vivid and compelling portrait of a life in science.”—Oliver Sacks
That I chose an academic career seems a bit odd, for I found both grade school and high school rather boring. I could get Bs with little effort, and those always seemed good enough. My parents never pushed me to do better, even though both of them had been A students.
My junior and senior high school was Walnut Hills High School in Cincinnati, Ohio. It was a college-preparatory public high school; you had to take a test in the sixth grade to gain admission. But Walnut Hills, as far as I could tell, was no better than elementary school: many of its teachers had been there for de cades and seemed to have little interest in capturing the attention of their students. Since we were required to take Latin for three years beginning in the seventh grade, my father decided to tutor me so that I could more easily grasp this arcane language. His tutelage helped, and Latin became one of my favorite subjects—once I had mastered the fundamentals. In fact, it was so easy that I took Latin for five years instead of adding a more useful language like French, a decision I'd later regret.
My high school experience with the sciences was somewhat different. I took advanced-placement math courses my senior year, but my homeroom teacher, who taught chemistry, would not allow me to take AP chemistry. When my parents complained, he told them that I would never be able to comprehend the science. Instead, I took the non-AP chemistry course and wound up tutoring many of my friends, who found the abstract thinking in chemistry difficult. Did I major in chemistry at the University of Pennsylvania just to prove my homeroom teacher wrong? Did I spend my life doing biochemical research in quest of his praise? A few psychiatrists might choose that interpretation, but I doubt that this high school rebuff had anything to do with my pursuit of chemistry. I enjoyed chemistry because I never had to memorize anything. The key was to balance the equations; I had to be sure that each side of the equation had the same number of hydrogen, carbon, nitrogen, oxygen, and sulfur atoms. Once my addition was correct, all I needed was some rudimentary knowledge of the process—though I have since learned that chemical research demands a bit more savvy and a lot more insight.
In spite of my uninspiring classes, I was enthusiastic about the Boy Scouts and my high school fraternity. I preferred scouting activities to those demanded of me as a student, and they provided an antidote for my boredom. I became an Eagle Scout and took summer jobs at the local scout camp. I even tried to postpone college by applying for a yearlong position as a Boy Scout–military aide at the U.S. Air Force base at Thule, Greenland. Only many years later, after a visit to the South Pole, did I realize how lucky I was to have been turned down.
Despite having never made it to Greenland, I retained an interest in cold temperatures. My first research experience began during the summer after my junior year at Penn, when I investigated the effects of hypothermia in retarding brain swelling in rats. The next summer, I pursued a project directed by Bernard Black-Schaffer at the University of Cincinnati, in which I studied the tolerance of hypothermic hamsters to acceleration forces of more than eight hundred times that of gravity, such as might be experienced during interstellar space travel. During medical school at Penn, I began studying the brown fat of hamsters during arousal from hibernation.
While my infatuation with cold temperatures was to end with my brown fat studies, my love of science grew. The privilege of spending time discovering something that no one else had ever known before became an insatiable thirst. As it happened, hamsters would continue to play a critical role in my research as the mysteries of the prion unfolded.
My Forebears ...
The roots of my love for science have always been mysterious to me. Neither of my parents was a scientist, but they must have bequeathed to me certain traits useful in that field. My father, Lawrence Albert Prusiner, was an architect with an aptitude for numbers, and my mother, Miriam Hannah Spigel, was imaginative, creative, and relentless in pursuing her passions (pottery, tropical fish, bonsai, ikebana). Both were descendants of Jewish immigrants from eastern Europe. To understand my parents better, I became obsessed with learning about our origins (figures 1–2).
My paternal great-grandfather Wulf Prusner (the i crept in later) was a prominent attorney in Moscow, which he left in the spring of 1891, shortly after its governor, the brother of Czar Alexander III, ordered the expulsion of Jews from the city. Permission to remain was given only to those who converted to Christianity, to those Jewish women willing to become prostitutes, and to those wealthy Jewish merchants and their families deemed useful to the city's economy. Altogether, more than fourteen thousand Jewish families were expelled from Moscow to the Pale of Settlement, a region of western Russia that included much of present-day Lithuania, Belarus, Poland, and Ukraine.
In Moscow, Wulf managed to obtain a passport from the German consul general. While his wife, Feine Moiseev, and their two sons and one daughter moved to Mogilev, the capital of eastern Byelorussia (Belarus), he traveled to Germany, intent on emigrating to the United States to make a better life for his family. He arrived in New York and made his way to Chicago, where he got a job rolling cigars. Learning that better jobs were available farther west, he moved on and by the end of 1891 he had reached Sioux City, Iowa, where there was a growing, vibrant Jewish community. The earliest Jewish settlers in Sioux City predate the Civil War. All were of German descent; the first Russian Jews arrived there in 1888, only three years before Wulf. There, he took a number of menial jobs: night watchman at a streetcar barn, janitor at a public library, fruit peddler. He went to night school to learn English; eventually he was to build an insurance business, which, having Anglicized his first name, he called the William L. Prusiner Insurance Company.
As an attorney in Moscow, Wulf had managed to amass the equivalent of more than $40,000 in assets, a small fortune in those times. When the Jews were expelled, he gave power of attorney to a trusted friend, who agreed to liquidate his properties and give the proceeds to Feine and their three children. A few months after her banishment to Mogilev, Feine and the children went back to Moscow to collect her husband's estate from his friend, who treacherously notified the police that they had returned to the city. A regiment of officials swooped down on them and thrust them into jail. For making a faint stand for her rights, Feine was fined the equivalent of $500. In a letter to her husband in Sioux City, she wrote that this was "all the money I had on earth." After paying the fine, Feine and her children were taken to the outskirts of Moscow and ordered to leave the country. Wulf sent his wife $125 for passage to America, and the family started for the German frontier, four days' journey by rail. When they reached the border, they were ordered back by sentries, who were there to stem the tide of Russian-Jewish refugees. It was a time of mass exodus: Every day, nearly four thousand Russian Jews tried to leave. In despair, Feine made her way back to Mogilev to wait.
According to a contemporary article in the Sioux City Journal, when two of Wulf's Sioux City friends lobbied for transit visas for Wulf's wife and children, they were told that "on account of the German regulations and quarantine laws, ... it [would be] impossible to accomplish anything." But they appealed to the U.S. State Department on Feine's behalf. Their effort was rewarded in March 1893, when Secretary of State Walter Gresham received a dispatch from the American legation in Berlin: The German government had granted Feine Prusiner and her children permission to pass through Germany. By mid-April, the family had left Hamburg on the ship California, arriving in New York at the end of the month. Shortly afterward, they were re united with Wulf in Sioux City.
Four years later, Wulf would bring his two sisters and his father, Lippman-David, to Sioux City. Lippman-David's father, Noach, is thought to have moved to Shklov on the Dnieper River from the town of Pruzhany, or Prusana, in western Byelorussia near the Lithuanian border. Presumably Noach had no surname, as was common for Jews living in the Pale. Toward the middle of the nineteenth century, that changed when the czar decreed that Jews had to take last names and that those living outside their birthplace could take the name of the town from which they came. It was probably Noach who chose the name Prusner, which has the Yiddish ending "ner"; Russian officials would probably have given him a "sky" or "ski" instead.
Benjamin, the eldest child of Wulf and Feine Prusiner, was my grandfather. He never finished high school; he was forced to work to help his family survive. Eventually he built a small firm, the Benjamin W. Prusiner Insurance Company, in Des Moines. Benjamin's wife, my paternal grandmother, Ethel Galinsky, was born in Omaha, Nebraska, in 1884 and died at age thirty-two of a pulmonary embolism, four years after giving birth to my father and two years after delivering his brother, Stanley Arnold.
On my mother's side, my grandfather was also named Benjamin. His father, Moses Herman Spigel, and mother, Sarah Weinstein, were both born in Austria but moved to Romania, where they farmed tobacco before being encouraged by the State of Virginia to immigrate. In the Richmond area, Moses farmed tobacco for many years and brought his father, Benjamin, and mother, Fannie Betseig, from Austria. Moses and Sarah had eleven children; my grandfather Benjamin Spigel was the oldest of nine boys and was born on Christmas 1878, on shipboard as his parents and his sister Hannah crossed the Atlantic. After raising their family in Richmond, Moses and Sarah moved to Norfolk, where their son Benjamin had built a successful jewelry business and become a member of the city council. I never met my grandfather Benjamin Spigel because he was killed in a streetcar accident at age fifty; at that time, my mother was only fourteen years old. She had adored her father, and her memories of him remained vivid and indelible for six de cades. On the day of his death, the family's rabbi wrote:
The loss of Benjamin Spigel ... produced a void that cannot be filled.... To him came the orphan and the widow, the sorrowful and the oppressed, the ill and the troubled, for aid in their perplexing problems. To him came Jew and Gentile, big and little, for the sort of help that comes not only from the purse but also from the heart.... Benjamin Spigel was not only Norfolk's finest Jew and citizen; he was one of God's noblemen.... He was an ambassador of hope and an apostle of human love.
Benjamin Spigel's wife, Mollie, was my beloved maternal grandmother; she was born in 1887 in Salisbury, North Carolina, the second of six children of Jacob and Leah Feldman, both of whom came from Vilnius, Lithuania, at the end of the nineteenth century. When Jacob came to New York, he encountered the same problem as Wulf Prusiner had: too many immigrant Jews and not enough jobs. Jacob went south, to Baltimore, to stay with a cousin, but no jobs would be found there either. Encouraged to go farther south, he bought a horse and a wagon on whose sides were painted the words "Feldman and Sons," so Jacob took the name "Feldman" from his wagon. None of his descendants know what his surname was in Lithuania or the name he used when he entered the United States. Like many eastern Europe an Jews, Jacob and Leah wanted to forget a life that was harsh and filled with state-sponsored anti-Semitic violence. Jacob built a thriving dry goods business, with six stores in North Carolina and southern Virginia, but lost nearly everything in the Depression. My mother grew up in Norfolk; after her father's untimely death, there was enough money to send her to Hollins College, but only for two years.
My father, on the other hand, graduated from Iowa State University and received a master's degree in architecture from Harvard. Though jobs were scarce in the Depression, he found work as an architect in Washington, D.C., where he met my mother, who was working as a secretary. They postponed their marriage for more than a year when my father's brother developed Hodgkin's disease. His stepmother demanded that my father return to Des Moines to care for his dying brother. Eventually, he and my mother married on February 18, 1939, and settled in Des Moines, where I was born on May 28, 1942. I was named for my dead uncle Stanley Arnold but rather considerately given the middle name Ben so my initials would not be S.A.P.
Shortly afterward, my parents moved to Boston so that my father, who had enlisted when the Second World War broke out, could attend Naval Officer Candidate School before being sent to the island of Eniwetok, in the South Pacific. At that point, my mother took me to Cincinnati and moved into the same ten-story, red brick Presidential apartment building on Greenwood Avenue as her mother, Mollie Spigel. The hallways were filled with the stale odors of cooked food from kitchens that had little or no ventilation. Our small two-room apartments—my mother and I lived on the seventh floor and my grandmother on the fifth—had pull-down Murphy beds that were stored by day in shallow closets. The proximity of my grandmother's apartment was my great fortune. Whenever my mother became cross with me, which was rare, I needed only to go down two floors to see my loving grandmother. In her eyes, I could do no wrong! Moreover, for several years I didn't have to share either of these two women, both of whom doted on me. Their unconditional love created a level of self-confidence that was probably responsible for the work I was able to accomplish in later life. My father was overseas for two years, allowing me to be the little man of the house.
I still hold many loving memories of Granny. Her homemade chicken soup was fantastic—a recipe passed on to my mother. She and my mother read to me every day for hours; there were no television sets. Remembering my love for these two women who gave so much of themselves to me can still bring tears to my eyes. And the deep sadness I felt at age twelve when Granny died at sixty-seven of a hypertensive cerebral hemorrhage is among the most vivid of my childhood recollections.
During the war, my grandfather Ben Prusiner would sometimes visit us on Saturday mornings for brunch; he lived seventy-five miles away in Springfield, Ohio, where he managed a dry goods business and struggled to maintain his insurance business in Des Moines. My mother would prepare a sumptuous meal, of which the constant was pickled herring immersed in sour cream topped with chopped onions and capers. Whether the herring was layered on toasted bagels or slices of rye bread is a detail that escapes me; perhaps my love of toasted poppy seed bagels has its origin in those brunches with my grandfather. Ben died at the age of sixty-five, after his second heart attack.
Shortly after my father's return from the South Pacific, we moved back to Des Moines. Two months after my brother Paul's birth in 1948, my mother was hospitalized for many weeks. Her absence created an unfillable void in my world; I had just turned six. Two years later, she suffered her first heart attack, at age thirty-four. She was hospitalized for several months, during which I was allowed to see her only once and Paul, at age two, was not permitted to enter the hospital at all. I missed her terribly—she was the center of my world, her voice and smile bringing me so much joy and warmth. My father's love couldn't fill the emptiness created by her absence. My father visited her every day and had to care for us as well—which may have contributed to his relative lack of success as an architect. He was a selfless man who cared deeply about his family.
For the next forty years, I was to remain concerned about my mother's health. Her illness was never far from the minds of her husband and two sons. I have no doubt that the tenuousness of my mother's existence shaded our views of life. This uncertainty intensified the problems emanating from my father's inability to find a high-paying job as an architect. He and my mother struggled each month to pay their bills; rarely were they able to save any money. Both of my parents remained frustrated by their modest resources, but neither knew how to break out of the situation. They felt trapped.
Excerpted from MADNESS AND MEMORY by STANLEY B. PRUSINER. Copyright © 2014 Stanley B. Prusiner, M.D.. Excerpted by permission of Yale UNIVERSITY PRESS.
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